Methanone, 1,1'-(1,4-phenylene)bis[1-(4-phenoxyphenyl)-

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

1,4-phenylene bis[(4-phenoxyphenyl)-methanone]; [4-(4-phenoxybenzoyl)phenyl](4-phenoxyphenyl)methanone ( 54299-17-1) does not exhibit In vitro gene mutation toxicity by gene mutation assay as well as by In vitro mammlian cell gene mutation assay.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Experimental data of read across substances

Justification for type of information:

Weight of evidence approach based on structurally similar chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

WoE report is based on two in-vitro gene toxicity studies
1.This study was performed to investigate the potential of test item to induce gene mutations in comparison to vehicle control according to the plate incorporation test (Trial I) and the pre-incubation test (Trial II) using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102.
2.To evaluate the mutagenic potential of test chemical in Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA by AMES test.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

other:

Species / strain / cell type:

bacteria, other: Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA

Details on mammalian cell type (if applicable):

Not specified

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

No data

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced S9 metabolic activation system

Test concentrations with justification for top dose:

1.0 (NC), 0 (VC), 0.003, 0.008, 0.025, 0.079 and 0.250 mg/plate
2; 0,.313, 625, 1250, 2500, 5000µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
1 Justification for choice of solvent/vehicle: The test chemical was solulble in DMSO
2.

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

sodium azide

methylmethanesulfonate

other: 4-Nitro-o-phenylenediamine (TA 1537, TA 98, without S9); 2-Aminoanthracene (TA 1535, TA 1537, TA 98, TA 100 and TA 102, with S9)

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

yes

Positive controls:

yes

Positive control substance:

other: -S9 mix, AF-2 (TA100, TA98), sodium azide (TA1535), ENNG (WP2 uvrA) and 9-aminoacridine (TA1537) +S9 mix, 2-aminoanthracene (all strains)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation- Trial I); preincubation (Trial II)

DURATION
- Preincubation period: Trial I: Not applicable Trial II: 60 min
- Exposure duration: 48 hrs
- Expression time (cells in growth medium): 48 hrs
- Selection time (if incubation with a selection agent): No data
- Fixation time (start of exposure up to fixation or harvest of cells): No data

SELECTION AGENT (mutation assays): No data

SPINDLE INHIBITOR (cytogenetic assays): No data

STAIN (for cytogenetic assays): No data

NUMBER OF REPLICATIONS: Each concentration, including the negative, vehicle and positive controls was tested in triplicate in two independent experiments performed

METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED: Not applicable

NUMBER OF CELLS EVALUATED: No data

NUMBER OF METAPHASE SPREADS ANALYSED PER DOSE (if in vitro cytogenicity study in mammalian cells): No data

CRITERIA FOR MICRONUCLEUS IDENTIFICATION: No data

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data
- Any supplementary information relevant to cytotoxicity: No data

OTHER EXAMINATIONS:
- Determination of polyploidy: No data
- Determination of endoreplication: No data
- Methods, such as kinetochore antibody binding, to characterize whether micronuclei contain whole or fragmented chromosomes (if applicable): No data

- OTHER: No data


2.Details on test system and conditions
METHOD OF APPLICATION: Preincubation method
NUMBER OF REPLICATIONS: Duplicate

OTHER EXAMINATIONS: 3 plates per test were observed.

Rationale for test conditions:

No data

Evaluation criteria:

A test item is considered as a mutagen, if a biologically relevant increase in the number of revertants exceeding the threshold of twice (strains TA 98, TA 100 and TA 102) or thrice (strains TA 1535 and TA 1537) the colony count of the corresponding vehicle/solvent control is observed.

A dose dependent increase is considered biologically relevant if the threshold is exceeded at more than one concentration.

An increase exceeding the threshold at only one concentration is judged as biologically relevant if reproduced in an independent second experiment.

A dose dependent increase in the number of revertant colonies below the threshold is regarded as an indication of a mutagenic potential if reproduced in an independent second experiment. However, whenever the colony counts remain within the historical range of negative control and vehicle control such an increase is not considered biologically relevant.

Statistics:

No data

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

bacteria, other: Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

1,TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: No data
- Effects of osmolality: No data
- Evaporation from medium: No data
- Water solubility: No data
- Precipitation: No data
- Definition of acceptable cells for analysis: No data
- Other confounding effects: No data

RANGE-FINDING/SCREENING STUDIES: To evaluate the toxicity of the test item, a pre-experiment was performed with strains TA 98 and TA 100. Eight concentrations (0, 0, 0.001, 0.003, 0.008, 0.025, 0.079, 0.250, 0.791 and 2.5 mg/plate ) were tested for toxicity and mutation induction with 3 plates each (triplicates). Toxicity of the test item results in a reduction in the number of spontaneous revertants or a clearing of the bacterial background lawn.

In the pre-experiment, the concentration range of the test item was 0.001 – 2.5 mg/plate based on the solubility and precipitation test. There was no reduction in colony count but reduction in background lawn was observed in treated concentrations 2.5 mg/plate (T8), 0.791 mg/plate (T7) both in absence and in the presence of metabolic activation and no reduction in colony count as well as in background lawn in treated concentrations (0.250 (T6) mg/plate – 0.001 (T1) mg/plate) both in absence and in the presence of metabolic activation. Based on the results of pre-experiment following doses were selected for the main study trials: (0, 0, 0.003, 0.008, 0.025, 0.079 and 0.250 mg/plate, both in the absence (-S9) as well as in the presence of metabolic activation (+S9).

CYTOKINESIS BLOCK (if used)
- Distribution of mono-, bi- and multi-nucleated cells: No data

NUMBER OF CELLS WITH MICRONUCLEI
- Number of cells for each treated and control culture: No data
- Indication whether binucleate or mononucleate where appropriate: No data

HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: No data
- Negative (solvent/vehicle) historical control data: No data

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: No data
- Other observations when applicable: No data

2.ADDITIONAL INFORMATION ON CYTOTOXICITY: No cytotoxicity was observed up to a concentration of 5000 µg/plate with or without metabolic activation.

Remarks on result:

other: No mutagenic potential

Conclusions:

1,4-phenylene bis[(4-phenoxyphenyl)-methanone]; [4-(4-phenoxybenzoyl)phenyl](4-phenoxyphenyl)methanone ( 54299-17-1) does not exhibit gene mutation toxicity.

Executive summary:

An in vitro bacterial gene mutation study was designed and conducted to determine the genotoxicity profile of 1,4-phenylene bis[(4-phenoxyphenyl)-methanone]; [4-(4-phenoxybenzoyl)phenyl](4-phenoxyphenyl)methanone (54299-17-1) When administered to bacteria. The studies are mention below

Ames assay was performed to investigate the potential of test substance  to induce gene mutations in comparison to vehicle control according to the plate incorporation test (Trial I) and the pre-incubation test (Trial II) using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102. The assay was performed in two independent experiments both with and without liver microsomal activation. Each concentration, including the negative, vehicle and positive controls was tested in triplicate. Based on the solubility and precipitation test results eight different concentrations viz.,0 (NC), 0, (VC) 0.001, 0.003, 0.008, 0.025, 0.079, 0.250, 0.791 and 2.5 mg/plate were selected for pre-experiment. Based on the pre-experiment results, the test item was tested with the following concentrations 0 (NC), 0 (VC), 0.003, 0.008, 0.025, 0.079 and 0.250 mg/plate for main study, both in the presence of metabolic activation (+S9) and in the absence of metabolic activation (-S9). No substantial increase in revertant colony numbers in any of the tester strains were observed following treatment with Methyl-2-napthyl ether (CAS no. 93-04-9) at any dose level in both the confirmatory trials, neither in the presence nor in the absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance.The spontaneous reversion rates in the negative, vehicle and positive controls are within the range of our historical data. The spontaneous reversion rates in the negative, vehicle and positive controls were within the range of in house historical data. Whereas reference mutagens showed a distinct increase in induced revertant colonies in all the tester strains both in the presence as well as in the absence of metabolic activation without showing cytotoxicity. In conclusion, it is stated that during the described mutage­nicity test and under the experimental conditions reported, the test substance did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.

Genetic toxicity in vitro study was assessed for test substance. For this purpose AMES test was performed according to: OECD guideline (No. 471, 472) and Guidelines for Screening Mutagenicity Testing of Chemicals (Japan).The test material was exposed to Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA in the presence and absence of metabolic activation S9. The concentration of test material used in the presence and absence of metabolic activation were0, 313, 625, 1250, 2500, 5000 µg/plate. No mutagenic effects were observed in all strains, in the presence and absence of metabolic activation. Therefore test chemical was considered to be non-mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA by AMES test. Hence the substance cannot be classified as gene mutant in vitro.

Reference 2

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Experimental data of read across substances

Justification for type of information:

Weight of evidence approach based on structurally similar chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

WoE report is based on two in-vitro gene toxicity studies
1. In vitro mammalian chromosome aberration test was performed to determine the test chemical
2.In vitro mammalian chromosome aberration test was performed to determine the mutagenic nature of the test chemical

GLP compliance:

not specified

Type of assay:

other: In vitro mammalian chromosome aberration test

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Remarks:

CHO-W-B1, 1

Details on mammalian cell type (if applicable):

- Type and identity of media: McCoy’s 5a medium supplemented with 10% fetal calf serum, L-glutamine,
and antibiotics.- Properly maintained: No data available- Periodically checked for Mycoplasma cont
amination: No data available- Periodically checked for karyotype stability: No data available- Peri
odically "cleansed" against high spontaneous background: No data available

Additional strain / cell type characteristics:

not specified

Species / strain / cell type:

mammalian cell line, other: Chinese hamster bone marrow cells

Remarks:

2.

Details on mammalian cell type (if applicable):

not specified

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not specified

Metabolic activation:

with and without

Metabolic activation system:

The S9 mix consisted of 15 μl/ml liver homogenate (from male Sprague-Dawley rats, induced with Arocl or 1254), 2.4 mg/ml NADP, and 4.5 mg/ml isocitric acid in serum-free medium.

Test concentrations with justification for top dose:

1.0.04-0.8 μg/mL
2.500, 1000 or 2000 mg/Kg

Vehicle / solvent:

1.- Vehicle(s)/solvent(s) used: Ethanol - Justification for choice of solvent/vehicle: The chemical was soluble in ethanol.

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

cyclophosphamide

mitomycin C

other: Triethylenemelamine

Remarks:

1.

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

2.

Details on test system and experimental conditions:

1. METHOD OF APPLICATION: In mediumDURATION- Preincubation period: No data available- Exposure duration: Cells were exposed to the test chemical for 2 hr in the presence of S9 or for 20 hrs without S9.-
Expression time (cells in growth medium): 28.5 – 37.3 hrs during the delayed harvest time- Selection time (if incubation with a selection agent): No data available- Fixation time (start of exposure up to fixation or harvest of cells): The cell harvest time for the aberration test was 8-12 hr after the beginning of treatme nt. This yielded cells in their first mitosis. Depending on the amount of delay seen in the SCE test, later harvest times, eg, 28.5 – 37.3 hr, were used to allow delayed cells to reach mitosis.SELECTION AGENT (mutation assays): No data availableSPINDLE INHIBITOR (cytogenetic assays): No data availableSTAIN (for cytogenetic assays): GiemsaNUMBER OF REPLICATIONS: No data availableNUMBER OF CELLS
EVALUATED: 100 cells were scored from each of the three highest dose groups having sufficient meta phases for analysisDETERMINATION OF CYTOTOXICITY- Method: mitotic index; cloning efficiency; relative total growth; other: No data availableOTHER EXAMINATIONS:- Determination of polyploidy: No data available- Determination of endoreplication: No data available- Other: No dataOTHER: No data available.

2. METHOD OF APPLICATION: in medium
DURATION
- Preincubation period: No data
- Exposure duration: No data
- Expression time (cells in growth medium): No data
- Selection time (if incubation with a selection agent): No data
- Fixation time (start of exposure up to fixation or harvest of cells): No data
SELECTION AGENT (mutation assays): No data
SPINDLE INHIBITOR (cytogenetic assays): No data
STAIN (for cytogenetic assays): No data
NUMBER OF REPLICATIONS: No data
NUMBER OF CELLS EVALUATED: No data
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data
OTHER EXAMINATIONS:
- Determination of polyploidy: No data
- Determination of endoreplication: No data
- Other:
OTHER: No data

Evaluation criteria:

1. All types of aberrations were recorded separately, but for data analysis they were grouped into categories of “simple” (breaks and terminal deletions), “complex” (exchanges and rearrangements), “other” (includes pulverized chromosomes), and “total. ” Gaps and endoreduplications were recorded but were not included in the totals. We did not score aberrations in polyploidy cells but used metaphases with 19-23 chromosomes (the modal number being 21).

2. The cell line was observed for chromatid breaks, chromatid exchanges, acentric fragments, pulverisations, etc. and anomolous interphase cells

Statistics:

1. Linear regression analysis of the percentage of cells with aberrations vs the log-dose was used as the test for trend. To examine absolute increases over control levels at each dose, a binomial sampling assumption (as opposed to Poisson) was used. The P values were adjusted by Dunnett’s method to take into account the multiple dose comparisons. For data analysis, we used the “total” aberration category, and the criterion for a positive response was that the adjusted P value be < 0.05.

Species / strain:

Chinese hamster Ovary (CHO)

Remarks:

CHO-W-B1, 1

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

mammalian cell line, other: Chinese hamster bone marrow cells

Remarks:

2.

Metabolic activation:

not specified

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

1. TEST-SPECIFIC CONFOUNDING FACTORS- Effects of pH: No data available- Effects of osmolality: No data available
- Evaporation from medium: No data available- Water solubility: No data available- Precipitation: No data available- Other confounding effects: No available data
RANGE-FINDING/SCREENING
STUDIES: Dose selection was based on a preliminary growth inhibition test in which cells that excluded trypan blue were counted 24 hr after treatment. The top doses selected for the cytogenetics assays were those estimated to reduce growth by 50%. This approach was subsequently modified such that toxicity estimates were made from observations of cell monolayer confluence and mitotic activity in the same cultures used for analysis of SCEs or aberrations. In some cases, test chemical precipitate was observed at the higher dose levels. Dose selection for repeat trials involved a range of doses based on observations from the first trial.

COMPARISON WITH HISTORICAL CONTROL DATA: No data available
ADDITIONAL INFORMATION ON CYTOTOXICITY: No data available

Remarks on result:

other: Non mutagenic

Conclusions:

1,4-phenylene bis[(4-phenoxyphenyl)-methanone]; [4-(4-phenoxybenzoyl)phenyl](4-phenoxyphenyl)methanone ( 54299-17-1) does not exhibit gene mutation toxicity.

Executive summary:

Chromosome aberration:

An in vitro mammalian cell gene mutation study was designed and conducted to determine the genotoxicity profile of 1,4-phenylene bis[(4-phenoxyphenyl)-methanone]; [4-(4-phenoxybenzoyl)phenyl](4-phenoxyphenyl)methanone (54299-17-1) When administered to Chinese Hamster Ovary (CHO) cells. 

Study 1:

An in vitro mammalian chromosome aberration test was performed to determine the mutagenic nature of test chemical using Chinese hamster ovary cells (CHO-W-B1) at dose levels of 0.04- 0.8 µg/mL. Cells were exposed to the test chemical for 2 hr in the presence of S9 or for 20hrs without S9 and were incubated for 28.5 – 37.3 hrs during the delayed harvest time. One hundred cells were scored from each of the three highest dose groups having sufficient metaphases for analysis. Based on the results noted, test chemical failed to induce chromosome aberrations in the Chinese hamster ovary cells (CHO-W-B1) in the presence and absence of S9 metabolic activation system, and hence is not classified as a gene mutant in vitro.

Study 2:

In vitro mammalian chromosome aberration test was performed to determine the mutagenic nature of the test chemical. The study was performed using Chinese hamster bone marrow cells. The test chemical was tested at dose levels of 500, 1000 or 2000 mg/Kg and cyclophosphamide at 128 mg/kg was used as the positive control chemical. The treated cell line wad scored for aberrant metaphases (chromatid break, chromatid exchanges, acentric fragments, pulverisations, etc.) and anomolous interphase cells. The test chemical did not cause a significant enhancement of the aberrant metaphases or of anomalous interphase cells in the Chinese hamster bone marrow cells and hence it is not likely to classify as a gene mutant in vitro.

Based on the data available for 2 ,2'-(ethene-1,2-diyldi-4,1-phenylene)bis(1,3-benzoxazole) (CAS no 1533-45-5)does not exhibit gene toxicity toxicity. Hence the test chemical is not likely to classify as in-vitro gene toxicity as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Data for the various test chemicals was reviewed to determine the mutagenic nature of 1,4-phenylene bis[(4-phenoxyphenyl)-methanone]; [4-(4-phenoxybenzoyl)phenyl](4-phenoxyphenyl)methanone (54299-17-1) . The studies are as mentioned below:

 

AMES test;

Ames assay was performed to investigate the potential of test substance  to induce gene mutations in comparison to vehicle control according to the plate incorporation test (Trial I) and the pre-incubation test (Trial II) using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102. The assay was performed in two independent experiments both with and without liver microsomal activation. Each concentration, including the negative, vehicle and positive controls was tested in triplicate. Based on the solubility and precipitation test results eight different concentrations viz.,0 (NC), 0, (VC) 0.001, 0.003, 0.008, 0.025, 0.079, 0.250, 0.791 and 2.5 mg/plate were selected for pre-experiment. Based on the pre-experiment results, the test item was tested with the following concentrations 0 (NC), 0 (VC), 0.003, 0.008, 0.025, 0.079 and 0.250 mg/plate for main study, both in the presence of metabolic activation (+S9) and in the absence of metabolic activation (-S9). No substantial increase in revertant colony numbers in any of the tester strains were observed following treatment with Methyl-2-napthyl ether (CAS no. 93-04-9) at any dose level in both the confirmatory trials, neither in the presence nor in the absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance.The spontaneous reversion rates in the negative, vehicle and positive controls are within the range of our historical data. The spontaneous reversion rates in the negative, vehicle and positive controls were within the range of in house historical data. Whereas reference mutagens showed a distinct increase in induced revertant colonies in all the tester strains both in the presence as well as in the absence of metabolic activation without showing cytotoxicity. In conclusion, it is stated that during the described mutage­nicity test and under the experimental conditions reported, the test substance did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.

Genetic toxicity in vitro study was assessed for test substance. For this purpose AMES test was performed according to: OECD guideline (No. 471, 472) and Guidelines for Screening Mutagenicity Testing of Chemicals (Japan).The test material was exposed to Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA in the presence and absence of metabolic activation S9. The concentration of test material used in the presence and absence of metabolic activation were0, 313, 625, 1250, 2500, 5000 µg/plate. No mutagenic effects were observed in all strains, in the presence and absence of metabolic activation. Therefore test chemical was considered to be non-mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA by AMES test. Hence the substance cannot be classified as gene mutant in vitro.

 In vitro Mammalian cell gene mutation assay

An in vitro mammalian chromosome aberration test was performed to determine the mutagenic nature of test chemical using Chinese hamster ovary cells (CHO-W-B1) at dose levels of 0.04- 0.8 µg/mL. Cells were exposed to the test chemical for 2 hr in the presence of S9 or for 20hrs without S9 and were incubated for 28.5 – 37.3 hrs during the delayed harvest time. One hundred cells were scored from each of the three highest dose groups having sufficient metaphases for analysis. Based on the results noted, test chemical failed to induce chromosome aberrations in the Chinese hamster ovary cells (CHO-W-B1) in the presence and absence of S9 metabolic activation system, and hence is not classified as a gene mutant in vitro.

 

In vitro mammalian chromosome aberration test was performed to determine the mutagenic nature of the test chemical. The study was performed using Chinese hamster bone marrow cells. The test chemical was tested at dose levels of 500, 1000 or 2000 mg/Kg and cyclophosphamide at 128 mg/kg was used as the positive control chemical. The treated cell line wad scored for aberrant metaphases (chromatid break, chromatid exchanges, acentric fragments, pulverisations, etc.) and anomolous interphase cells. The test chemical did not cause a significant enhancement of the aberrant metaphases or of anomalous interphase cells in the Chinese hamster bone marrow cells and hence it is not likely to classify as a gene mutant in vitro.

 

Based on the data summarized, 1,4-phenylene bis[(4-phenoxyphenyl)-methanone]; [4-(4-phenoxybenzoyl)phenyl](4-phenoxyphenyl)methanone (54299-17-1)did not induce gene mutation .Hence it is not likely to be mutagenic in vitro.

Justification for classification or non-classification

Thus based on the above annotation and CLP criteria for target substance 1,4-phenylene bis[(4-phenoxyphenyl)-methanone]; [4-(4-phenoxybenzoyl) phenyl](4-phenoxyphenyl)methanone (54299-17-1) did not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.